What are the recommendations for low-dose aspirin (acetylsalicylic acid) therapy as a long-term preventive measure for patients at high risk of cardiovascular events?

Low-Dose Aspirin for Long-Term Cardiovascular Prevention

For secondary prevention in patients with established atherosclerotic cardiovascular disease (ASCVD), aspirin 75-162 mg daily should be used indefinitely—the benefits overwhelmingly outweigh bleeding risks. For primary prevention, aspirin is only reasonable in select patients aged 40-59 years with ≥10% 10-year CVD risk and low bleeding risk, but should NOT be initiated in adults ≥60 years. 1, 2, 3

Secondary Prevention: Strong Recommendation

Aspirin 75-162 mg daily is mandatory for all patients with established ASCVD including prior myocardial infarction, stroke, coronary revascularization, or documented obstructive coronary artery disease. 1, 2 The evidence here is unequivocal:

• Absolute risk reduction of 33 cardiovascular events per 1,000 patients treated over 33 months, with 12 fewer nonfatal MIs, 25 fewer strokes, and 14 fewer deaths. 4
• The 21% relative risk reduction in serious vascular events (HR 0.79) far exceeds the bleeding risk in this population. 4, 5
• Use 75-100 mg daily as the optimal dose—higher doses provide no additional cardiovascular benefit but significantly increase bleeding complications. 1, 2

After acute coronary syndrome, dual antiplatelet therapy (aspirin plus P2Y12 inhibitor like clopidogrel) is required for at least 1 year, then transition to aspirin monotherapy indefinitely. 1, 2

For patients with documented aspirin allergy, substitute clopidogrel 75 mg daily. 1, 3

Primary Prevention: Highly Selective Use Only

The 2019 American Diabetes Association guidelines and 2022 USPSTF recommendations fundamentally shifted the primary prevention paradigm based on recent trials (ARRIVE, ASPREE) showing no net benefit and increased bleeding. 1, 6

Age-Based Algorithm for Primary Prevention:

Adults aged 40-59 years:

• Only consider aspirin if 10-year ASCVD risk ≥10% AND low bleeding risk. 3, 6
• For diabetic patients ≥50 years with ≥1 additional major risk factor (hypertension, dyslipidemia, smoking, family history of premature ASCVD, or chronic kidney disease/albuminuria), aspirin 75-162 mg daily may be considered. 1, 2
• The absolute benefit is small: aspirin prevents approximately 6-10 cardiovascular events per 1,000 patients over 5 years, but causes 2-5 major bleeding events. 1, 5

Adults aged ≥60 years:

• Do NOT initiate aspirin for primary prevention, regardless of cardiovascular risk. 3, 6
• The ASPREE trial definitively showed no cardiovascular benefit (HR 0.95% CI 0.83-1.08) but significantly increased major hemorrhage (HR 1.38,95% CI 1.18-1.62). 1
• For patients over age 70, bleeding risks clearly exceed any potential cardiovascular benefit. 1

Adults aged <40 years or <50 years without risk factors:

• Aspirin is NOT recommended—the low absolute cardiovascular risk makes bleeding risks unacceptable. 1

Bleeding Risk Assessment: Critical Before Initiating Therapy

Absolute contraindications to aspirin: 2, 3

• Active bleeding or recent gastrointestinal bleeding
• Known bleeding disorder or thrombocytopenia
• Documented aspirin allergy
• Concurrent anticoagulation therapy
• Age <21 years (Reye syndrome risk) 1

High bleeding risk factors that preclude aspirin use: 1, 2

• Uncontrolled hypertension (BP >150/90 mmHg)
• History of gastrointestinal ulcers
• Anemia
• Chronic kidney disease
• Concurrent NSAID or corticosteroid use
• Older age (≥70 years)

The excess bleeding risk is approximately 5 per 1,000 patients per year in real-world settings, with major gastrointestinal bleeding being the primary concern (relative risk 2.11). 1

Optimal Dosing Strategy

Use 75-100 mg daily (81 mg in the US) for all indications. 1, 2, 7 This is the lowest effective dose that:

• Provides complete inhibition of thromboxane A2-dependent platelet aggregation 1
• Maintains full cardiovascular protection equivalent to higher doses 2, 4
• Minimizes gastrointestinal toxicity and bleeding complications 1

For acute coronary syndromes or acute ischemic stroke, give a loading dose of 160-300 mg immediately, then transition to 75-100 mg daily for long-term therapy. 1

Doses >162 mg provide no additional cardiovascular benefit but substantially increase bleeding risk—avoid them. 3

Special Populations

Diabetic patients with established ASCVD:

• Aspirin 75-162 mg daily is mandatory for secondary prevention. 1, 2
• The cardiovascular benefits are particularly robust in this high-risk population. 1

Hypertensive patients:

• Blood pressure must be controlled (<150/90 mmHg) before initiating aspirin to minimize hemorrhagic stroke risk. 2
• The HOT trial showed 15% reduction in cardiovascular events and 36% reduction in MI with aspirin 75 mg daily in well-controlled hypertensive patients. 2

Women vs. Men:

• In primary prevention, aspirin reduces MI in men but not women, while reducing stroke in women but not men. 2
• For secondary prevention, benefits are equivalent regardless of sex. 5

Common Pitfalls to Avoid

1. Do not prescribe aspirin for primary prevention in adults ≥60 years—this is now explicitly recommended against based on recent high-quality evidence. 3, 6

2. Do not use doses >162 mg for chronic prevention—higher doses only increase bleeding without improving efficacy. 3

3. Do not initiate aspirin in patients with uncontrolled hypertension—control blood pressure first to avoid hemorrhagic complications. 2

4. Do not discontinue aspirin in patients with established ASCVD—the secondary prevention benefit is overwhelming and non-negotiable. 1, 2

5. Do not assume all diabetic patients need aspirin—only those with established ASCVD or very high primary prevention risk with low bleeding risk qualify. 1